ALTERNATIVE SPLICE VARIANT OF THE THIAZIDE-SENSITIVE NaCl COTRANSPORTER: A NOVEL PLAYER IN RENAL SALT HANDLING.

ALTERNATIVE SPLICE VARIANT OF THE THIAZIDE-SENSITIVE NaCl COTRANSPORTER: A NOVEL PLAYER IN RENAL SALT HANDLING. Am J Physiol Renal Physiol. 2015 Nov 11;:ajprenal.00429.2015 Authors: Tutakhel OA, Jeleń S, Valdez-Flores M, Dimke H, Piersma SR, Jimenez CR, Deinum J, Lenders JW, Hoenderop JG, Bindels RJ Abstract The thiazide-sensitive NaCl cotransporter (NCC) is an important pharmacological target in the treatment of hypertension. Human SLC12A3 gene, encoding NCC, gives rise to three isoforms. Only the 3(rd) isoform has been extensively investigated. The aim of the present study was, therefore, to establish the abundance and localization of the almost identical isoforms 1 and 2 (NCC1/2) in the human kidney and to determine their functional properties and regulation in physiological conditions. Immunohistochemical analysis of NCC1/2 in the human kidney revealed that NCC1/2 localizes to the apical plasma membrane of the distal convoluted tubule. Importantly, NCC1/2 mRNA constitutes approximately 44% of all NCC isoforms in the human kidney. Functional analysis performed in the Xenopus laevis oocyte revealed that thiazide-sensitive (22)Na(+) transport of NCC1 was significantly increased in comparison to NCC3. Mimicking a constitutively active phosphorylation site at residue 811 (S811D) in NCC1 further augmented Na(+) transport, while a non-phosphorylatable variant (S811A) of NCC1 prevented this enhanced response. Analysis of human urinary e...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research